Periportal hepatotoxicity due to allyl alcohol: A myriad of proposed mechanisms

Abstract

AbstractIt has long been recognized that periportal and centrilobular regions of the liver lobule differ in their sensitivity to many hepatotoxins. For example, carbon tetrachloride damages centrilobular regions while allyl alcohol damages periportal areas of the liver lobule (1). One determinant of the selective susceptibility of different areas of the liver lobule to chemically induced injury is believed to be the sublobular distribution of enzymes involved in detoxification, or activation to more toxic metabolites (2–4). In addition to sublobular enzyme activity, substrate delivery and the availability of necessary cofactors can influence the zone‐specific toxicity of some chemicals. Furthermore, it has been proposed that oxygen gradient across the liver lobule is an important determinant of zonal hepatotoxicity. Thus, studies regarding the zone‐specific nature of hepatotoxicants require that a variety of complex interrelated metabolic processes be considered, and so far exact mechanisms responsible for zone‐selective hepatotoxicity are not completely understood.